Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Neonatal outcomes of extremely preterm infants exposed to maternal hypertension and cigarette smoking

Journal of Perinatology volume 38, pages 1051–1059 (2018)Cite this article

Subjects

Abstract

Objective:

To study the outcomes of extremely preterm infants of hypertensive mothers who smoke.

Study design:

This retrospective cohort study included infants born between 2003 and 2012 at <29 weeks’ gestation and admitted to neonatal intensive care units participating in the Canadian Neonatal Network. Infants were divided into four mutually exclusive groups. Infants of hypertensive mothers who smoked; infants of hypertensive, non-smoking mothers; infants of normotensive mothers who smoked; and infants of normotensive, non-smoking mothers. Using infants of normotensive, non-smoking mothers as the reference group, neonatal outcomes were compared between the groups. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were calculated using univariate and multivariate regression analysis.

Results:

Of the 12,307 eligible infants, 172 had hypertensive mothers who smoked, 1689 had hypertensive non-smoking mothers, 1535 had normotensive mothers who smoked, and 8911 had normotensive non-smoking mothers. Compared to infants of normotensive non-smoking mothers, infants of hypertensive mothers, regardless of smoking status, had higher odds of developing bronchopulmonary dysplasia (AORs of smokers 1.62; 95% CI 1.12–2.35 and of non-smokers 1.43; 95% CI 1.24–1.64). There was no difference in the odds of mortality and retinopathy of prematurity stage ≥3 between the groups. Infants of hypertensive, non-smoking mothers had decreased odds of intraventricular hemorrhage >grade 2 and higher odds of necrotizing enterocolitis. There was decreased odds of hypertension if the mother was a smoker (AOR 0.71; 95% CI 0.59–0.85).

Conclusion:

Maternal hypertension is associated with increased rates of bronchopulmonary dysplasia, irrespective of smoking status.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. American College of Obstetricians and Gynecologists, Task Force on Hypertension in Pregnancy. Hypertension in pregnancy: Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013;122:1122–31.

  2. Umesawa M, Kobashi G. Epidemiology of hypertensive disorders in pregnancy: prevalence, risk factors, predictors and prognosis. Hypertens Res. 2017;40:213–20.

    Article  PubMed  Google Scholar 

  3. Hutcheon JA, Lisonkova S, Joseph KS. Epidemiology of pre-eclampsia and the other hypertensive disorders of pregnancy. Best Pract Res Clin Obstet Gynaecol. 2011;25:391–403.

    Article  PubMed  Google Scholar 

  4. Gemmell L, Martin L, Murphy KE, Modi N, Hakansson S, Reichman B, et al. Hypertensive disorders of pregnancy and outcomes of preterm infants of 24 to 28 weeks’ gestation. J Perinatol. 2016;36:1067–72.

    Article  CAS  PubMed  Google Scholar 

  5. Rugolo LMSS, Bentlin MR, Trinade CEP. Preeclampsia: early and late neonatal outcomes. NeoReviews. 2012;13:e532–41.

    Article  Google Scholar 

  6. Sjaus A, McKeen DM, George RB. Hypertensive disorders of pregnancy. Can J Anaesth. 2016;63:1075–97.

    Article  PubMed  Google Scholar 

  7. Sieminska A, Jassem E. The many faces of tobacco use among women. Med Sci Monit. 2014;20:153–62.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Abbott LC, Winzer-Serhan UH. Smoking during pregnancy: lessons learned from epidemiological studies and experimental studies using animal models. Crit Rev Toxicol. 2012;42:279–303.

    Article  CAS  PubMed  Google Scholar 

  9. Isayama T, Shah PS, Ye XY, Dunn M, Da Silva O, Alvaro R, et al. Adverse impact of maternal cigarette smoking on preterm infants: a population-based cohort study. Am J Perinatol. 2015;32:1105–11.

    Article  PubMed  Google Scholar 

  10. Mei-Dan E, Walfisch A, Weisz B, Hallak M, Brown R, Shrim A. The unborn smoker: association between smoking during pregnancy and adverse perinatal outcomes. J Perinat Med. 2015;43:553–8.

    Article  PubMed  Google Scholar 

  11. Downard CD, Grant SN, Maki AC, Krupski MC, Matheson PJ, Bendon RW, et al. Maternal cigarette smoking and the development of necrotizing enterocolitis. Pediatrics. 2012;130:78–82.

    Article  PubMed  Google Scholar 

  12. Ng M, Freeman MK, Fleming TD, Robinson M, Dwyer-Lindgren L, Thomson B, et al. Smoking prevalence and cigarette consumption in 187 countries, 1980-2012. JAMA. 2014;311:183–92.

    Article  CAS  PubMed  Google Scholar 

  13. Gudnadottir TA, Bateman BT, Hernadez-Diaz S, Luque-Fernandez MA, Valdimarsdottir U, Zoega H. Body mass index, smoking and hypertensive disorders during pregnancy: a population based case-control study. PLoS ONE. 2016;11:e0152187.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Voigt M, Neudecker K, Schneider KT, Olbertz D, Briese V, Straube W, et al. Effects of smoking specified as cigarettes per day and maternal body mass index on hypertensive disorders of pregnancy. Z Geburtshilfe Neonatol. 2013;217:24–7.

    Article  CAS  PubMed  Google Scholar 

  15. Miller EC, Cao H, Wu Wen S, Yang Q, Lafleche J, Walker M. The risk of adverse pregnancy outcomes is increased in preeclamptic women who smoke compared with nonpreeclamptic women who do not smoke. Am J Obstet Gynecol. 2010;203:334.e1–8.

    Article  Google Scholar 

  16. Cnattingius S, Mills JL, Yuen J, Eriksson O, Salonen H. The paradoxical effect of smoking in preeclamptic pregnancies: smoking reduces the incidence but increases the rates of perinatal mortality, abruptio placentae, and intrauterine growth restriction. Am J Obstet Gynecol. 1997;177:156–61.

    Article  CAS  PubMed  Google Scholar 

  17. Pipkin FB, on behalf of the genetics of preeclampsia consortium. Smoking in moderate/severe preeclampsia worsens pregnancy outcome, but smoking cessation limits the damage. Hypertension. 2008;51:1042–6.

    Article  CAS  PubMed  Google Scholar 

  18. Lee SK, McMillan DD, Ohlsson A, Pendray M, Synnes A, Whyte R, et al. Variations in practice and outcomes in the Canadian NICU network: 1996-7. Pediatrics. 2000;106:1070–9.

    Article  CAS  PubMed  Google Scholar 

  19. Shah PS, Seidlitz W, Chan P, Yeh S, Musrap N, Lee SK, et al. Internal audit of the Canadian Neonatal Network Data Collection System. Am J Perinatol. 2017;34:1241–9.

    Article  PubMed  Google Scholar 

  20. The Canadian Neonatal Network. Abstractor’s Manual v.2.1.1 2013. http://wwwcanadianneonatalnetworkorg/portal/CNNHome/Publicationaspx.

  21. Shennan AT, Dunn MS, Ohlsson A, Lennox K, Hoskins EM. Abnormal pulmonary outcomes in premature infants: prediction from oxygen requirement in the neonatal period. Pediatrics. 1988;82:527–32.

    CAS  PubMed  Google Scholar 

  22. Papile LA, Munsick-Bruno G, Schaefer A. Relationship of cerebral intraventricular hemorrhage and early childhood neurologic handicaps. J Pediatr. 1983;103:273–7.

    Article  CAS  PubMed  Google Scholar 

  23. Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L, et al. Neonatal necrotizing enterocolitis - therapeutic decisions based upon clinical staging. Ann Surg. 1978;187:1–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Gole G, Ells A, Katz X, Holmstrom G, Fielder A, Capone A, et al. The International Classification of Retinopathy of Prematurity Revisited. Arch Ophathlmology. 2005;123:991–9.

    Article  Google Scholar 

  25. Morse S, Groer M, Shelton MM, Maguire D, Ashmeade T. A systematic review: the utility of the revised version of the score for neonatal acute physiology among critically ill neonates. J Perinat Neonatal Nurs. 2015;29:315–44, quiz E312

    Article  PubMed  PubMed Central  Google Scholar 

  26. Beste LA, England LJ, Schisterman EF, Qian C, Yu KF, Levine RJ. Pregnancy outcome in smokers who develop preeclampsia. Paediatr Perinat Epidemiol. 2005;19:12–18.

    Article  PubMed  Google Scholar 

  27. Levine RJ, Hauth JC, Curet LB, Sibai BM, Catalano PM, Morris CD, et al. Trial of calcium to prevent preeclampsia. N Engl J Med. 1997;337:69–76.

    Article  CAS  PubMed  Google Scholar 

  28. Morrow LA, Wagner BD, Ingram DA, Poindexter BB, Schibler K, Cotten CM, et al. Antenatal determinants of bronchopulmonary dysplasia and late respiratory disease in preterm infants. Am J Respir Crit Care Med. 2017;196:364–74.

    Article  PubMed  PubMed Central  Google Scholar 

  29. EXPRESS Group. Incidence of and risk factors for neonatal morbidity after active perinatal care: extremely preterm infants study in Sweden (EXPRESS). Acta Paediatr. 2010;99:978–92.

    Article  Google Scholar 

  30. Hebel JR, Fox NL, Sexton M. Dose-response of birth weight to various measures of maternal smoking during pregnancy. J Clin Epidemiol. 1988;41:483–9.

    Article  CAS  PubMed  Google Scholar 

  31. Blatt K, Moore E, Chen A, Van Hook J, DeFranco EA. Association of reported trimester-specific smoking cessation with fetal growth restriction. Obstet Gynecol. 2015;125:1452–9.

    Article  PubMed  PubMed Central  Google Scholar 

  32. McEvoy CT, Spindel ER. Pulmonary effects of maternal smoking on the fetus and child: effects on lung development, respiratory morbidities, and life long lung health. Paediatr Respir Rev. 2017;21:27–33.

    PubMed  Google Scholar 

  33. Spindel ER, McEvoy CT. The role of nicotine in the effects of maternal smoking during pregnancy on lung development and childhood respiratory disease. Implications for dangers of E-cigarettes. Am J Respir Crit Care Med. 2016;193:486–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Burke H, Leonardi-Bee J, Hashim A, Pine-Abata H, Chen Y, Cook DG, et al. Prenatal and passive smoke exposure and incidence of asthma and wheeze: systematic review and meta-analysis. Pediatrics. 2012;129:735–44.

    Article  PubMed  Google Scholar 

  35. Hoo AF, Henschen M, Dezateux C, Costeloe K, Stocks J. Respiratory function among preterm infants whose mothers smoked during pregnancy. Am J Respir Crit Care Med. 1998;158:700–5.

    Article  CAS  PubMed  Google Scholar 

  36. Bi GL, Chen FL, Huang WM. The association between hypertensive disorders in pregnancy and bronchopulmonary dysplasia: a systematic review. World J Pediatr. 2013;9:300–6.

    Article  PubMed  Google Scholar 

  37. Chaiworapongsa T, Chaemsaithong P, Yeo L, Romero R. Pre-eclampsia. Part 1: Current understanding of its pathophysiology. Nat Rev Nephrol. 2014;10:466–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Wang A, Holston AM, Yu KF, Zhang J, Toporsian M, Karumanchi SA, et al. Circulating anti-angiogenic factors during hypertensive pregnancy and increased risk of respiratory distress syndrome in preterm neonates. J Matern Fetal Neonatal Med. 2012;25:1447–52.

    Article  CAS  PubMed  Google Scholar 

  39. Hadchouel A, Franco-Montoya ML, Delacourt C. Altered lung development in bronchopulmonary dysplasia. Birth Defects Res A Clin Mol Teratol. 2014;100:158–67.

    Article  CAS  PubMed  Google Scholar 

  40. Sheffield M, Mabry S, Thibeault DW, Truog WE. Pulmonary nitric oxide synthases and nitrotyrosine: findings during lung development and in chronic lung disease of prematurity. Pediatrics. 2006;118:1056–64.

    Article  PubMed  Google Scholar 

  41. Andersen MR, Simonsen U, Uldbjerg N, Aalkjaer C, Stender S. Smoking cessation early in pregnancy and birth weight, length, head circumference, and endothelial nitric oxide synthase activity in umbilical and chorionic vessels: an observational study of healthy singleton pregnancies. Circulation. 2009;119:857–64.

    Article  PubMed  Google Scholar 

  42. Ali SM, Khalil RA. Genetic, immune and vasoactive factors in the vascular dysfunction associated with hypertension in pregnancy. Expert Opin Ther Targets. 2015;19:1495–515.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Doshi H, Moradiya Y, Roth P, Blau J. Variables associated with the decreased risk of intraventricular haemorrhage in a large sample of neonates with respiratory distress syndrome. Arch Dis Child Fetal Neonatal Ed. 2016;101:F223–9.

    Article  PubMed  Google Scholar 

  44. Perlman JM, Risser RC, Gee JB. Pregnancy-induced hypertension and reduced intraventricular hemorrhage in preterm infants. Pediatr Neurol. 1997;17:29–33.

    Article  CAS  PubMed  Google Scholar 

  45. Bashiri A, Zmora E, Sheiner E, Hershkovitz R, Shoham-Vardi A, Mazor M. Maternal hypertensive disorders are an independent risk factor for the development of necrotizing enterocolitis in very low birth weight infants. Fetal Diagn Ther. 2003;18:404–7.

    Article  PubMed  Google Scholar 

  46. Cetinkaya M, Ozkan H, Koksal N. Maternal preeclampsia is associated with increased risk of necrotizing enterocolitis in preterm infants. Early Hum Dev. 2012;88:893–8.

    Article  PubMed  Google Scholar 

  47. Gray PH, Rodwell RL. Neonatal neutropenia associated with maternal hypertension poses a risk for nosocomial infection. Eur J Pediatr. 1999;158:71–3.

    Article  CAS  PubMed  Google Scholar 

  48. Gagliardi L, Rusconi F, Bellu R, Zanini R, Italian Neonatal Network. Association of maternal hypertension and chorioamnionitis with preterm outcomes. Pediatrics. 2014;134:e154–61.

    Article  PubMed  Google Scholar 

  49. Chen XK, Wen SW, Smith G, Yang Q, Walker M. Pregnancy-induced hypertension and infant mortality: roles of birthweight centiles and gestational age. BJOG. 2007;114:24–31.

    Article  CAS  PubMed  Google Scholar 

  50. Jain L. Effect of pregnancy-induced and chronic hypertension on pregnancy outcome. J Perinatol. 1997;17:425–7.

    CAS  PubMed  Google Scholar 

  51. Goland RS, Jozak S, Warren WB, Conwell IM, Stark RI, Tropper PJ. Elevated levels of umbilical cord plasma corticotrophin-releasing hormone in growth-retarded fetuses. J Clin Endocrinol Metab. 1993;77:1174–9.

    CAS  PubMed  Google Scholar 

  52. Rasmussen S, Irgens LM. The effects of smoking and hypertensive disorders on fetal growth. BMC Pregnancy Childbirth. 2006;6:16.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Pereira PP, Da Mata FA, Figueiredo AC, de Andrade KR, Pereira MG. Maternal active smoking during pregnancy and low birth weight in the Americas: a systematic review and meta-analysis. Nicotine Tob Res. 2017;19:497–505.

    Article  PubMed  Google Scholar 

  54. Fitzgerald K, Cai J, Hoff G, Dew P, Okah F. Clinical manifestation of small-for-gestational-age risk pregnancy from smoking is gestational age dependent. Am J Perinatol. 2007;24:519–24.

    Article  PubMed  Google Scholar 

  55. Klebanoff MA, Levine RJ, Clemens JD, DerSimonian R, Wilkins DG. Serum cotinine levels and self-reported smoking during pregnancy. Am J Epidemiol. 1998;148:259–62.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors gratefully acknowledge all site investigators of the CNN. We extend our thanks to the data abstractors of the CNN and the staff at the Maternal-Infant Care Research Centre at Mount Sinai Hospital, Toronto, Ontario for providing organizational support for this project. We thank Philip Ye for statistical analysis. We also thank Sarah Hutchinson, PhD, from the Maternal-Infant Care Research Centre for editorial assistance in the preparation of this manuscript. PSS is supported by an Applied Research Chair in Reproductive, Child and Youth Health Services and Policy research from the Canadian Institutes of Health Research.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

    Kamran Yusuf, Belal Alshaikh & Abhay K. Lodha

  2. Department of Pediatrics, University of Western Ontario, London, ON, Canada

    Orlando da Silva

  3. Department of Obstetrics and Gynecology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

    Robert D. Wilson

  4. Department of Pediatrics, University of Manitoba, Winnipeg, MB, Canada

    Ruben E. Alvaro

  5. Department of Pediatrics, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada

    Shoo K. Lee & Prakesh S. Shah

Authors
  1. Kamran Yusuf
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Belal Alshaikh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Orlando da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Abhay K. Lodha
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Robert D. Wilson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ruben E. Alvaro
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shoo K. Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Prakesh S. Shah
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

on behalf of the Canadian Neonatal Network Investigators

Corresponding author

Correspondence to Kamran Yusuf.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Group information: A full list of the investigators in the Canadian Neonatal Network can be found in the Appendix.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yusuf, K., Alshaikh, B., da Silva, O. et al. Neonatal outcomes of extremely preterm infants exposed to maternal hypertension and cigarette smoking. J Perinatol 38, 1051–1059 (2018). https://doi.org/10.1038/s41372-018-0111-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41372-018-0111-1

This article is cited by

Search

Advanced search

Quick links